1. Field of the Invention
The instant invention relates to a novel cytokine. In particular, a purified monocyte derived insulin receptor regulatory factor, which has a biological activity of reducing insulin receptor binding on T-lymphocytes, is provided and characterized. Additionally, provided are methods of altering insulin receptor binding on T-lymphocytes.
2. Background Art
The insulin receptor is a non-constitutive membrane bound heterodimer found on the lymphocyte surface which is a marker of lymphocyte activation by antigen or lectin (1-3), indicates the ontogenetic state of that cell (14), and is the vehicle by which the growth factor insulin subserves its immunobiologic roles (1,4-7). We have demonstrated that regulation of the insulin receptor itself is the means by which the lymphocyte is variously responsive to ambient levels of the hormone insulin which is under separate, non-immunologically mediated control (15). The means by which the insulin receptor is regulated, then, becomes important in understanding lymphocyte responsiveness to hormonal manipulations.
We recently have characterized three distinct mechanisms for such regulation: 1) the provision of a signal to initiate reading of the insulin receptor gene sequence (1,13); 2) the regulation of the number of copies of receptors once synthesized by binding of the ligand to its receptor and internalization of the ligand-receptor complex (16); 3) alteration in the number of copies of receptor molecules synthesized as a function of ambient insulin as signaled by monocytes (7,10,11,17). The latter mechanism is unique to the immune system, resembles the cell-cell interaction by which Antigen Presenting Cells (APC) cooperate with T-lymphocytes for the presentation of such environmental signals as antigen, and cannot involve ligand binding since the monocyte-derived signals are provided at a time when lymphocytes are insulin receptor negative.
Knowledge of the regulation of the insulin receptor on activated lymphocytes permits a fuller understanding of the means by which insulin subserves its signal function with respect to the lymphocyte activation cascade. There thus exists a need to isolate and characterize regulators of the insulin receptor and to study their biological activity. This invention satisfies this need by providing a purified regulator of the insulin receptor.